1,721,055 research outputs found
Unraveling microbubble-cell interactions and drug delivery mechanisms in ultrasound-guided therapy
No full textTowards the clinical evaluation of Galsome-NEO, a glycolipid-adjuvanted mRNA cancer vaccine
No full textDesign and evaluation of immunotherapeutic imaging for cancer vaccination
Get PDFCancer immunotherapy, where a patient's immune system is harnessed in the battle against a tumor, is currently on the rise. One possible approach comprises the in vitro modulation of dendritic cells with tumor antigens, after which the cells are injected as a therapeutic cancer vaccine. Despite extensive progress and promising (pre)clinical results, such cancer vaccines often remain patient-specific, laborious in production and therefore very expensive. In this thesis, these issues are addressed by developing imageable biomaterials as cancer immunotherapeutics. Firstly, we highlight the use of antigen-loaded perfluorocarbon particles for 19F MRI tracking of dendritic cells is explored. Such imageable cellular vaccines could provide information on the fate and migratory potential of the cells after their injection, and therefore give important initial feedback on the vaccine efficacy. Secondly, we investigated an alternative strategy that makes use of mRNA-loaded microbubbles for ultrasound-guided and ultrasound-triggered immune activation. We demonstrated that this principle could indeed be used to induce antigen expression in dendritic cells in vitro. Moreover, by simultaneously delivering both antigen mRNA and adjuvant mRNA (TriMix), highly immunogenic dendritic cell vaccines could be produced, allowing complete tumor regression in 30% of the vaccinated animals, which were protected against tumor recurrence. Interestingly, these mRNA-loaded microbubbles show potential for the immediate in vivo delivery of mRNA to dendritic cells as they spontaneously migrate to the lymph nodes upon subcutaneous injection. What is more, the image feedback information provided by these contrast agents on the lymphatic anatomy underpins their interesting role as immunotheranostic agents
Design and evaluation of drug loaded microbubbles for ultrasound guided cancer therapy
Get PDFCancer is a genetic disease, caused by mutations in the genome of normal cells. Chemical and physical damage to the cellular genome can induce these mutations resulting in the transformation of a healthy cell into a tumor cell. Over the past years, researchers have acquired a basic understanding of tumor onset. Several important proto-oncogenes and proteins involved in angiogenesis have been identified, leading to the development and clinical use of several new anticancer agents.
We succeeded in preparing microbubbles which are able to carry genetic (pDNA, siRNA) and chemotherapeutic (doxorubicin) drugs. We proved that these microbubbles can selectively deliver their genetic or chemotherapeutic drugs to melanoma cells upon ultrasound exposure. We also showed that the activity of currently available drug carriers (pDNA or siRNA lipoplexes and doxorubicin-liposomes) was significantly improved by microbubble coupling and ultrasound exposure. This enables us to obtain a space and time controlled drug delivery guided by ultrasound. The fact that ultrasound and microbubbles have already been approved for ultrasound contrast imaging and are currently used in daily clinic, makes it very plausible that the microbubble concept reported in this thesis may find its way as an advanced drug delivery system
Exploring novel drug delivery strategies in rheumatoid arthritis : nanomedicines and ultrasound triggered drug delivery
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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